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  GnRH (Factrel)
 
Author: Donna Karasic, PharmD Last modified: February 21, 2002
 

  INDICATIONS

  • Evaluation of hypothalamic/pituitary gonadotropic function
  • Hypothalamic Amenorrhea
  • Male Infertility (non-FDA approved use)
  • Female Infertility (non-FDA approved use)
  • Measure Pituitary Gonadotropin Reserve (non-FDA approved use)
  • Puberty Induction (non-FDA approved use)

  DOSAGE

  • Evaluation of hypothalamic/pituitary gonadotropic function: 100 mcg administered SQ or IV; samples of FSH & LH at 0,30,60,90min (rarely used)
  • Amenorrhea: 5 mcg IV every 90 minutes using gonadorelin 0.8 milligram/8 milliliters at 50 microliters/pulse in the Lutrepulse Pump. Treatment interval is 21 days
  • Female Infertility: 5 to 20 mcg every 90 minutes, injected by a programmed infusion pump.
  • Male infertility: continuous infusion of 1 mcg/minute for 180 min was used in men with idiopathic oligospermia; rarely used; replaced w/ HCG intramuscularly three times weekly

  PHARMACOKINETICS

  • Peak levels of luteinizing hormone (given IV): 13.5 to 25 minutes
  • Peak levels of luteinizing hormone (given SC):decreased by approximately 75% to 95% and may be further impaired by obesity
  • Time to peak concentration is 1.2 to 3 minutes (given IV)
  • Elimination half-life is 10 to 40 minutes

  ADVERSE EFFECTS

  • Headache
  • Lightheadedness
  • Multiple follicle development and multiple pregnancy
  • Ovarian hyperstimulation
  • Redness and swelling at the injection site
  • Allergic reactions that are mediated by immunoglobulin E antibody have been reported

  CONTRAINDICATIONS

  • Hypersensitivity to gonadorelin or any of the components of the product
  • Any condition exacerbated by pregnancy
  • Ovarian cysts or causes of anovulation other than hypothalamic origin
  • Hormonally-dependent tumor
  • Conditions worsened by an increase of reproductive hormones

  DRUG INTERACTIONS

  • Clomiphene
  • Oral contraceptives
  • Menotropins

  FORMS

  • 100mcg and 500mcg vials; powder for injection

  MECHANISM OF ACTION

  • Gonadorelin binds to specific transmembrane glycoprotein receptors on gonadotrophic cells of the anterior pituitary
  • Binding to these receptors stimulates synthesis and secretion of gonadotropins through mobilization of intracellular calcium, activation of protein kinase C, and gene transcription
  • The continuous administration of gonadorelin results in desensitization of gonadotrophic cells through receptor uncoupling, receptor sequestration, and gonadotropin stores depletion
 
IMPORTANT POINTS/RECOMMENDATIONS
  • Gonadorelin test should not be conducted in patients who are concurrently receiving drugs which directly affect the pituitary secretion of gonadotropin.
  • Multiple pregnancy is possible with ovulation induction
  • The infusion area must be monitored for signs of infection or irritation.
 
REFERENCES
  1. Hutchinson TA & Shahan DR (Eds) ;  Gonadorelin ;  MICROMEDEX Healthcare Series; MICROMEDEX, Greenwood Village, Colorado (edition expires 3-2002)

Copyright © 2002 The Johns Hopkins University School of Medicine. All rights reserved.